TY - JOUR
T1 - Differentiation and roles of bone marrow-derived cells on the tumor microenvironment of oral squamous cell carcinoma
AU - Anqi, Chang
AU - Takabatake, Kiyofumi
AU - Kawai, Hotaka
AU - May Wathone, O. O.
AU - Yoshida, Saori
AU - Fujii, Masae
AU - Omori, Haruka
AU - Sukegawa, Shintaro
AU - Nakano, Keisuke
AU - Tsujigiwa, Hidetsugu
AU - Jinhua, Zheng
AU - Nagatsuka, Hitoshi
N1 - Funding Information:
The presen study was funded by Japanese Society for Promotion of Science KAKENHI Grant-in-Aid for Scientific Research (grant nos. 18K09789, 18K17224, 16K20577 and 19K19160).
Funding Information:
The presen study was funded by Japanese Society for Promotion of Science KAKENHI Grant‑in‑Aid for Scientific Research (grant nos. 18K09789, 18K17224, 16K20577 and 19K19160).
Publisher Copyright:
© 2019 Spandidos Publications. All rights reserved.
PY - 2019
Y1 - 2019
N2 - The stroma affects the properties and dynamics of the tumor. Previous studies have demonstrated that bone marrow-derived cells (BMDCs) possess the capability of differentiating into stromal cells. However, the characteristics and roles of BMDCs in oral squamous cell carcinoma remain unclear. The current study therefore investigated their locations and features by tracing green fluorescent protein (GFP)-labeled BMDCs in a transplantation mouse model. After irradiation, BALB-c nu-nu mice were injected with bone marrow cells from C57BL/6-BALB-C-nu/nu-GFP transgenic mice. These recipient mice were then injected subcutaneously in the head with human squamous cell carcinoma-2 cells. Immunohistochemistry for GFP, Vimentin, CD11b, CD31 and α-smooth muscle actin (SMA), and double-fluorescent immunohistochemistry for GFP-Vimentin, GFP-CD11b, GFP-CD31 and GFP-α-SMA was subsequently performed. Many round-shaped GFP-positive cells were observed in the cancer stroma, which indicated that BMDCs served a predominant role in tumorigenesis. Vimentin(+) GFP(+) cells may also be a member of the cancer-associated stroma, originating from bone marrow. Round or spindle-shaped CD11b(+) GFP(+) cells identified in the present study may be macrophages derived from bone marrow. CD31(+)GFP(+) cells exhibited a high tendency towards bone marrow-derived angioblasts. The results also indicated that spindle-shaped α-SMA(+) GFP(+) cells were not likely to represent bone marrow-derived cancer-associated fibroblasts. BMDCs gathering within the tumor microenvironment exhibited multilineage potency and participated in several important processes, such as tumorigenesis, tumor invasion and angiogenesis.
AB - The stroma affects the properties and dynamics of the tumor. Previous studies have demonstrated that bone marrow-derived cells (BMDCs) possess the capability of differentiating into stromal cells. However, the characteristics and roles of BMDCs in oral squamous cell carcinoma remain unclear. The current study therefore investigated their locations and features by tracing green fluorescent protein (GFP)-labeled BMDCs in a transplantation mouse model. After irradiation, BALB-c nu-nu mice were injected with bone marrow cells from C57BL/6-BALB-C-nu/nu-GFP transgenic mice. These recipient mice were then injected subcutaneously in the head with human squamous cell carcinoma-2 cells. Immunohistochemistry for GFP, Vimentin, CD11b, CD31 and α-smooth muscle actin (SMA), and double-fluorescent immunohistochemistry for GFP-Vimentin, GFP-CD11b, GFP-CD31 and GFP-α-SMA was subsequently performed. Many round-shaped GFP-positive cells were observed in the cancer stroma, which indicated that BMDCs served a predominant role in tumorigenesis. Vimentin(+) GFP(+) cells may also be a member of the cancer-associated stroma, originating from bone marrow. Round or spindle-shaped CD11b(+) GFP(+) cells identified in the present study may be macrophages derived from bone marrow. CD31(+)GFP(+) cells exhibited a high tendency towards bone marrow-derived angioblasts. The results also indicated that spindle-shaped α-SMA(+) GFP(+) cells were not likely to represent bone marrow-derived cancer-associated fibroblasts. BMDCs gathering within the tumor microenvironment exhibited multilineage potency and participated in several important processes, such as tumorigenesis, tumor invasion and angiogenesis.
KW - Bone marrow-derived cells
KW - Cancer stroma
KW - Green f luorescence protein transplanted mouse
KW - Oral cancer
KW - Tumor microenvironment
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U2 - 10.3892/ol.2019.11045
DO - 10.3892/ol.2019.11045
M3 - Article
AN - SCOPUS:85076283694
SN - 1792-1074
VL - 18
SP - 6628
EP - 6638
JO - Oncology Letters
JF - Oncology Letters
IS - 6
ER -